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HARN - Nanotech Regulatory Document Archive

HARN - Nanotech Regulatory Document Archive

decade after the

decade after the exposure, and that the highest levels of risk may not become apparent until 20 to 30 years after the exposure. The increasing risk is eventually curtailed by the competing effects of natural mortality from other causes. There has been some evidence (Macdonald et al, 2007) that the risks may not be as high as predicted from the model towards the end of the human lifespan e.g. at ages above about 70. In general, the epidemiological information points to relationships between an index of exposure (in terms of numbers of fibres as measured by the phase contrast optical microscope method) and the risk of disease. Hodgson and Darnton (2000) from their meta-analysis concluded that the risks of mesothelioma from chrysotile asbestos, amosite asbestos, and crocidolite asbestos, differed greatly relative to this index of exposure. Amosite was 100 times more potent than chrysotile, and crocidolite 500 times more potent than chrysotile. The amosite and crocidolite are both much more biopersistent in the human lung than chrysotile and that may be part of the explanation for the hundred fold difference. Crocidolite has finer diameter fibres (i.e. fibres with diameter less than 200 nano metres) and that may be part of the explanation for the difference between crocidolite and amosite. Timbrell (1989) reviewed the evidence on occurrence of mesothelioma in areas where amphibole asbestos was mined. His findings suggested that the areas where mesothelioma occurred were characterised by having a pattern of airborne fibres with diameters less than 200 nanometres. By contrast, where mesothelioma was apparently absent, the fibre distributions apparently were characterised by fibre diameters generally greater than 200 nanometres. Animal studies to investigate risks of mesothelioma have generally employed injection of fibres into the pleural or peritoneal cavities. Injection studies with glass fibres of different size distribution have demonstrated that fibres longer than about 8 µm produce much greater risk of mesothelioma than shorter fibres, e.g. the much quoted studies of Stanton and Wrench. However, the main caveat on these studies is that they rely on a non-physiological delivery (i.e. injection) of fibres into an internal body cavity. The diameter of fibres may be critical in determining whether inhaled fibres would reach the pleura or peritoneum. Where man made mineral fibres have diameters greater than 200 nano metres, there does not appear to be a risk of mesothelioma by inhalation. Pleural plaques are a benign condition associated with exposure to asbestos. They comprise fibres of collagen lying parallel to the surface of the pleura. Calcification may occur in the centre of the plaques. According to HSE guidance “Pleural plaques are discrete fibrous or partially calcified thickened areas, which arise from the surface of the parietal pleura and can be detected in chest X-ray or Computer Tomogram (CT) examination. Pleural plaques do not become malignant and do not normally cause impaired lung function.” However, the detection of pleural plaques in an individual is a sign of past asbestos exposure. Other Cancers There have been studies to assess whether ingestion of asbestos fibres leads to cancers of the gastrointestinal system. Most studies have not demonstrated a significant effect. However, one study (Andersen et al, 1993) in Norwegian light housekeepers who drank water collected from asbestos cement tile roofs which contained a high level of asbestos fibres in suspension (1,760 to 71,350 million fibres/litre of water) showed a significant excess (e.g. 2.4 fold) of stomach Page 10

cancers. However, Gamble (2007) in reviewing the evidence on occupational exposure to asbestos and lung cancer commented on this study that “The cause of the stomach excess is not certain because of possible confounders such as diet (many of the lighthouse keepers were retired seamen). Exposure is not well defined, as it is not known when the (asbestos cement) tiles began to deteriorate and the size of the cohort is small.” These comments indicate the difficulty of establishing causation of an excess of gastrointestinal cancer. Nevertheless, Anderson and associates (Kjærheim 2005) in a further report on the cohort concluded that “The results support the hypothesis of an association between ingested asbestos and gastrointestinal cancer risk in general and stomach cancer risk specifically”. Gamble (2007) concluded from his extensive review of the published studies that “The epidemiological evidence detracts from the hypothesis that occupational asbestos exposure increases the risk of stomach, colorectal, colon, and rectal cancer.” Therefore, the evidence from asbestos epidemiology suggests that suggests that gastrointestinal cancers from inhaled or ingested high aspect ratio nano particles may be unlikely but, if they did occur would be difficult to confirm (or disprove) as being exposure-related. The main conclusions drawn from this brief review of the evidence of health effects of fibres are: • The key characteristics of fibres that cause high risk of mesothelioma appear to be small diameter (e.g. less than 200 nanometres), length and durability; • The length that creates the greatest risk of mesothelioma may depend on the cell penetration properties of the fibre or high aspect ratio particle; • Mesothelioma or lung cancer are likely to occur many years after exposure, for asbestos normally after more than ten years and typically 20 to 3 years later, and the same would be expected if other high aspect ratio particles cause these diseases; • The history of diseases caused by occupational exposure to asbestos illustrates the difficulties in recognising and proving the causation of the diseases, and demonstrates the importance of recognising the hazards without waiting for epidemiological evidence; • The exposure response relationships estimated for mesothelioma and asbestos-related lung cancer show no threshold below which there is absolutely no risk. Predicted risk diminishes as exposure becomes lower, but it has not been possible to establish if there is a threshold below which the risk is zero. • Measuring concentrations in air of high aspect ratio nano particles with techniques that have adequate resolution capabilities (to detect the thinnest of fibres) will be important. The similarities in shape and durability between HARN and asbestos suggest that exposure to HARN may cause similar adverse health effects. HARN deposited in the lung, because of its length, may be able to translocate to the pleura and cause mesothelioma like asbestos. The lag time after exposure and the absence of the threshold level, as the hallmark of mesothelioma, would be also expected with HARN. Page 11

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